Endokannabinoide sistemaren parte-hartzea arratoien garuntxoaren jaio osteko garapenean
- Ianire Buceta
- Irantzu Rico-Barrio
- Jon Egaña-Huguet
- Svein Achicallende
- Itziar Terradillos
- Nagore Puente
- Leire Reguero
- Naiara Royo
- Itziar Bonilla-Del Río
- Aitor Medrano
- Juan Mendizabal-Zubiaga
- Sonia María Gómez-Urquijo
- Almudena Ramos
- Inmaculada Gerrikagoitia
- Pedro Grandes
- Izaskun Elezgarai
ISSN: 0214-9001
Year of publication: 2018
Issue: 34
Pages: 123-148
Type: Article
More publications in: Ekaia: Euskal Herriko Unibertsitateko zientzi eta teknologi aldizkaria
Abstract
The endocannabinoid system (ECS) is widely distributed throughout the or-ganism. This system influences brain development and suppresses neurotransmitter re-lease in the mature brain, thus contributing to brain circuit formation and neural com-munication. Because of methodological limitations, most investigations focused on the study of the embryo development have been carried out in cell culture. In the central nervous system, the ECS is highly expressed in the cerebellar cortex where it plays a crucial role in the postnatal development of the granule cells. However, little is known about how the precise localization of the components of the ECS takes place during the early postnatal development, which is needed for the correct wiring of the cerebellar circuits. In this study, we used high resolution immunoelectron microscopy to investi-gate the subcellular localization of the cannabinoid CB1 receptor and the main enzymes for the synthesis and degradation of the endocannabinoid 2-arachidonoyl-glycerol (2-AG), diacylglycerol lipase (DAGL-α) and monoacylglycerol lipase (MAGL), re-spectively, in the granule cells during the early postnatal development of the cerebel-lum. The CB1 receptor, DAGL-α and MAGL were localized at the granule cell axons, the parallel fibers, during granule cell migration and axon elongation occurring at early postnatal age. Moreover, CB1 receptor and DAGL-α immunoparticles were placed in the parallel fiber membranes, while MAGL labeling was at the parallel fiber mem-branes and cytoplasm. At postnatal day 12, when parallel fibers make already synapses with the Purkinje cell dendritic spines, the CB1 receptor exhibited the typical presynap-tic localization in parallel fiber terminal membranes, and MAGL was close to the membrane and in the cytoplasm of the parallel fiber terminals. However, DAGL-α was excluded from the parallel fiber terminals but it was expressed at postsynaptic sites. Al-together, the expression of CB1 receptors, DAGL-α, and MAGL in the granule cell parallel fibers starts at early stages of the postnatal development. Later on, the CB receptors and MAGL remain in the mature parallel fiber synapses, while DAGL-α disap-pears from them and switches to the postsynaptic dendritic spines of the Purkinje cells. These structural changes correlate with the functions in which the ECS is involved dur-ing postnatal development. Hence, the identification of the specific localization of the components of the ECS in the developing cerebellum is crucial for understanding the structural, functional and behavioral changes taking place in the brain by cannabis con-sume. Furthermore, this knowledge could be exploited therapeutically as the ECS ma-nipulation might have potential clinical applications in the treatment of brain diseases caused by abnormal development of the brain.